{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:19:55Z","timestamp":1773274795693,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cystathionine beta synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Betaine supplementation, which can lower tHcy by stimulating homocysteine remethylation to methionine, is often given to CBS deficient patients in combination with other treatments such as methionine restriction and supplemental B\u2010vitamins. However, the effectiveness of betaine supplementation by itself in the treatment of CBS deficiency has not been well explored. Here, we have examined the effect of a betaine supplemented diet on the <jats:italic>Tg\u2010I278T Cbs<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mouse model of CBS deficiency and compared its effectiveness to our previously published data using a methionine restricted diet. <jats:italic>Tg\u2010I278T Cbs<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice on betaine, from the time of weaning until for 240 days of age, had a 40 % decrease in mean tHcy level and a 137 % increase in serum methionine levels. Betaine\u2010treated <jats:italic>Tg\u2010I278T Cbs<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice also exhibited increased levels of betaine\u2010dependent homocysteine methyl transferase (BHMT), increased levels of the lipogenic enzyme stearoyl\u2010coenzyme A desaturase (SCD\u20101), and increased lipid droplet accumulation in the liver. Betaine supplementation largely reversed the hair loss phenotype in <jats:italic>Tg\u2010I278T Cbs<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> animals, but was far less effective than methionine restriction in reversing the weight\u2010loss, fat\u2010loss, and osteoporosis phenotypes. Surprisingly, betaine supplementation had several negative effects in control <jats:italic>Tg\u2010I278T Cbs<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice including decreased weight gain, lean mass, and bone mineral density. Our findings indicate that while betaine supplementation does have some beneficial effects, it is not as effective as methionine restriction for reversing the phenotypes associated with severe CBS deficiency in mice.<\/jats:p>","DOI":"10.1007\/s10545-015-9883-z","type":"journal-article","created":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T09:40:41Z","timestamp":1438335641000},"page":"39-46","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Betaine supplementation is less effective than methionine restriction in correcting phenotypes of CBS deficient mice"],"prefix":"10.1002","volume":"39","author":[{"given":"Sapna","family":"Gupta","sequence":"first","affiliation":[{"name":"Cancer Biology Program, Fox Chase Cancer Center Philadelphia PA 19111 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liqun","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Biology Program, Fox Chase Cancer Center Philadelphia PA 19111 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Warren D.","family":"Kruger","sequence":"additional","affiliation":[{"name":"Cancer Biology Program, Fox Chase Cancer Center Philadelphia PA 19111 USA"},{"name":"Fox Chase Cancer Center 333 Cottman Avenue Philadelphia PA 19111 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(69)80274-X"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.54B2.277"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20320"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071527"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-380568"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2003.12.041"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027598"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-120584"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-240770"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.9.12.3445"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.41.220.666"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.11.190"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","unstructured":"MacleanKN SikoraJ KozichV et al (2010)A novel transgenic mouse model of CBS\u2010deficient homocystinuria does not incur hepatic steatosis or fibrosis and exhibits a hypercoagulative phenotype that is ameliorated by betaine treatment.Mol Genet Metab.","DOI":"10.1016\/j.ymgme.2010.06.010"},{"key":"e_1_2_8_15_1","first-page":"2007","volume-title":"The metabolic basis of inherited disease","author":"Mudd SH","year":"2001"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90897.2008"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1542\/peds.37.3.502","article-title":"Early diagnosis and treatment of homocystinuria","volume":"37","author":"Perry 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